This study characterized the interactions of mineral trioxide aggregate with a synthetic tissue fluid composed of a neutral phosphate buffer saline solution and root canal dentin in extracted human teeth using inductively coupled plasma-atomic emission spectroscopy, scanning electron microscopy, energy dispersive X-ray analysis, and X-ray diffraction. Mineral trioxide aggregate exposed to synthetic tissue fluid at 37°C released its metallic constituents and produced precipitates with a composition and structure similar to that of hydroxyapatite [Ca 10 (PO4) 6 (OH) 2 -HA]. Endodontically prepared teeth filled with mineral trioxide aggregate and stored in synthetic tissue fluid at 37°C for 2 months produced at the dentin wall an adherent interfacial layer that resembled hydroxyapatite in composition. The authors conclude that Ca, the dominant ion released from mineral trioxide aggregate, reacts with phosphates in synthetic tissue fluid, yielding hydroxyapatite. The dentin-mineral trioxide aggregate interfacial layer results from a similar reaction. The sealing ability, biocompatibility, and dentinogenic activity of mineral trioxide aggregate is attributed to these physicochemical reactions. (MTA) is a mechanical mixture of three powder ingredients: Portland cement (75%), bismuth oxide (20%), and gypsum (5%) (1). It also contains trace amounts of SiO 2 , CaO, MgO, K 2 SO 4 and Na 2 SO 4 . The major component, Portland cement, is a mixture of dicalcium silicate, tricalcium silicate, tricalcium aluminate, and tetracalcium aluminoferrite. MTA is prepared as a mixture of powder and water and is used in a slurry form, which gradually hardens in the oral environment.Since its introduction as a root-end filling material in 1993, the use of MTA has expanded to many applications of root repair and bone healing (2-4). These applications include direct pulp capping, repair of root and furcation perforations, and apexification. A material for such applications should have the ability to seal the dental pulp from bacterial and chemical invasion, and the candidate material should be biocompatible to prevent toxicity and tissue irritability. Both in vitro and in vivo studies have shown that MTA fulfills these requirements quite satisfactorily. The superior sealing ability of MTA over conventional retrograde filling materials, such as amalgam, IRM, and Super EBA, has been demonstrated in numerous microleakage tests using dye, fluid, bacteria, and endotoxin infiltration techniques (5-10). Its excellent biocompatibility has been evidenced in several favorable biologic processes induced by MTA, namely, minimal toxicity and pulpal irritation, mild periapical inflammation, nonmutagenicity, cell adherence and growth, increased levels of alkaline phosphatase and osteocalcin, interleukin production (IL-6, IL-8), periodontal ligament attachment, cementum growth, and dentinal bridge formation (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).Studies on MTA have mainly examined its various biologic properties, but lit...